Summary of work: DNA repair enzymes are activated in response to DNA damage. Alterations in DNA repair enzyme function and thus the rate and extent of repair contribute to malignant transformation. Transcription of the gene encoding DNA polymerizing enzyme beta- polymerase, a repair enzyme, is shown to be inhibited by the human T-cell leukemia virus type I (HTLV-I) transactivator protein Tax. The resultant inhibition of DNA repair may lead to unrepaired chromosomal damage. Severe combined immunodeficient (SCID) mice have a mutation in the catalytic subunit of the DNA binding protein kinase that is involved in repair of double-strand breaks in DNA. To deter- mine if the protein is involved in repair of other types of breaks, we examined the ability of SCID cells to repair lesions introduced by ultraviolet light and X-ray irradiation. After ultraviolet irradiation, murine SCID fibroblast cell lines had 50% less repair of photoproducts in chromosomal DNA compared to a wildtype cell line, as shown by impaired cellular survival and decreased unscheduled DNA synthesis. SCID cells also had 50% less repair of ultraviolet damage in the transcribed dihydrofolate reductase and c-myc genes than wildtype cells. After gamma irradiation, SCID fibroblasts had 30% less repair of single-strand breaks than wildtype cells in the genes encoding immunoglobulin heavy and light chains.